Central Unit for Animal Research and Animal Welfare Affairs (ZETT) of the Heinrich-Heine-University of Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany.
Department of OB/GYN and REI (UniKiD), University Hospital Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
Reprod Biol Endocrinol. 2019 Mar 2;17(1):28. doi: 10.1186/s12958-019-0470-2.
Syndecan-1 is a heparan sulfate proteoglycan acting as a co-receptor for cytokines and growth factors mediating developmental, immunological and angiogenic processes. In human, the uteroplacental localization of Syndecan-1 and its reduced expression in pregnancy-associated pathologies, such as the intrauterine growth restriction, suggests an influence of Syndecan-1 in embryo-maternal interactions. The aim of the present study was to identify the effect of a reduced expression of Syndecan-1 on the reproductive phenotype of mice and their progenies.
Reproductive characteristics have been investigated using animals with reduced Syndecan-1 and their wildtype controls after normal mating and after vice versa embryo transfers. Female mice were used to measure the estrus cycle length and the weight gain during pregnancy, as well as for histological examination of ovaries. Male mice were examined for the concentration, motility, viability and morphology of spermatozoa. Organs like heart, lung, liver, kidney, spleen, brain and ovaries or testes and epididymis of 6-month-old animals were isolated and weighed. Statistical analyses were performed using two-tailed students t-test with P < .05 and P < .02, chi square test (P < .05) and Fisher's Exact Test (P < .05). A linear and a non-linear mixed-effects model were generated to analyze the weight gain of pregnant females and of the progenies.
Focusing on the pregnancy outcome, the Syndecan-1 reduced females gave birth to larger litters. However, regarding the survival of the offspring, a higher percentage of pups with less Syndecan-1 died during the first postnatal days. Even though the ovaries and the testes of Syndecan-1 reduced mice showed no histological differences and the ovaries showed a similar number of primary and secondary follicles and corpora lutea, the spermatozoa of Syndecan-1 reduced males showed more tail and midpiece deficiencies. Concerning the postnatal and juvenile development the pups with reduced Syndecan-1 expression remained lighter and smaller regardless whether carried by mothers with reduced Syndecan-1 or wildtype foster mothers. With respect to anatomical differences kidneys of both genders as well as testes and epididymis of male mice with reduced syndecan-1 expression weighed less compared to controls.
These data reveal that the effects of Syndecan-1 reduction are rather genotype- than parental-dependent.
硫酸乙酰肝素蛋白聚糖-1(Syndecan-1)作为细胞因子和生长因子的共受体,参与调节发育、免疫和血管生成过程。在人类中,Syndecan-1 在胎盘组织中的定位及其在与妊娠相关的疾病(如宫内生长受限)中的表达降低,提示其在胚胎-母体相互作用中具有重要作用。本研究旨在确定 Syndecan-1 表达降低对小鼠生殖表型及其后代的影响。
通过使用 Syndecan-1 表达降低的动物及其野生型对照进行正常交配和相反的胚胎移植,研究了生殖特征。雌性小鼠用于测量发情周期长度和妊娠期间体重增加,以及对卵巢进行组织学检查。雄性小鼠用于检查精子的浓度、活力、形态和活力。对 6 月龄动物的心脏、肺、肝、肾、脾、脑和卵巢或睾丸以及附睾进行分离和称重。使用双尾学生 t 检验(P<.05 和 P<.02)、卡方检验(P<.05)和 Fisher 精确检验(P<.05)进行统计分析。生成线性和非线性混合效应模型,以分析妊娠雌性和后代的体重增加。
在关注妊娠结局时,Syndecan-1 表达降低的雌性产下的幼崽数量更多。然而,就后代的存活率而言,较少 Syndecan-1 的幼崽在出生后的头几天内死亡率更高。尽管 Syndecan-1 表达降低的小鼠的卵巢和睾丸在组织学上没有差异,且卵巢中初级和次级卵泡以及黄体的数量相似,但 Syndecan-1 表达降低的雄性的精子尾部和中段缺陷更多。在产后和幼年期发育方面,无论由 Syndecan-1 表达降低的母亲还是野生型代孕母亲携带,表达降低的幼崽体重和体型均较小。与对照组相比,Syndecan-1 表达降低的雄性的肾脏以及雌性的肾脏和睾丸和附睾的重量较轻。
这些数据表明,Syndecan-1 降低的影响主要是由基因型而非亲代决定的。